N-{N-[N-(1,1-Dimethyl­ethoxy­carbon­yl)-l-leuc­yl]-N-methyl-l-leuc­yl}-N-methyl-l-leucine benzyl ester

The tripeptide title compound, C32H53N3O6, synthesized in 80% yield by coupling of N-methyl-l-leucine benzyl ester with tert-butoxy­carbonyl-l-leucyl-N-methyl-l-leucine at 273 K, conjugates through two amide linkages and includes two protecting groups: a tert-butyl­oxycarbonyl group at the C-tip and a benzyl group at the N-tip. A classical inter­molecular N—H⋯O hydrogen bond and a weak non-conventional inter­molecular C—H⋯O contact connect the mol­ecules, forming layers parallel to (001)

Identifying long-term stable refugia for dominant Castanopsis species of evergreen broad-leaved forests in East Asia: A tool for ensuring their conservation

Identifying and protecting refugia is a priority for conservation management under projected anthropogenic climate change. We have two main objectives: the first is to explore the spatial (East Asia) and temporal (Last Glacial Maximum to year 2070) distribution patterns of dominant Castanopsis species of evergreen broad-leaved forests, also the relation with their niche breadths; the second is to identify long-term stable refugia for preserving these species and provide a framework of conservation strategies. We find that there is an extraordinary richness with 32 dominant Castanopsis species, and they form both a geographically and climatically almost unbroken connection from ca. 5°N to 38°N, having thus ecological significance. During the Mid-Holocene and, particularly, the Last Glacial Maximum, the predicted suitable areas of the species as a whole were larger than those in the present. By 2070, potentially suitable areas with high richness of dominant Castanopsis species will be reduced by 94.5 % on average. No correlation between species niche breadths and distribution ranges is found, which could be due to regional climate stability. Mountains of southwestern and southern Yunnan in China are identified as climatically long-term stable refugia for 7¿9 Castanopsis species. We recommend that these refugia have the highest priority of conservation to prevent their extinction. Our suggested urgent measures include improving the effectiveness of currently protected Castanopsis species and expanding the network of protected areas to cover a larger fraction of the refugia, as well as ensuring Castanopsis species natural regeneration potential in fragmented and natural secondary forest areas.This study received financial support from the Major Program for Basic Research Project of Yunnan Province, China (202101BC070002), the Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China (2015FY210200-15), the Spanish Ministry of Science and Innovation (grant PID2020-119163GB-I00 funded by MCIN/AEI/10.13039/501100011033), the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan (JPMEERF20202002), and the Northeastern Research Institute of Petrified Wood and Mineral Resources, Nakhon Ratchasima Rajabhat University, Thailand.Keywords 1. Introduction 2. Materials and methods 2.1. Data collection and notations 2.2. Ecological niche modeling 2.3. Data analyses 3. Results 3.1. Dominant Castanopsis species in East Asia today: richness and distribution patterns 3.2. Richness of dominant Castanopsis species shaped by climate change 3.3. Niche groups and niche breadths of dominant Castanopsis species 3.4. Climatically long-term stable refugia 4. Discussion 4.1. Richness of dominant Castanopsis species shaped by climate change 4.2. Niche groups and niche breadths of dominant Castanopsis species 4.3. Long-term stable refugia and conservation strategies 5. Conclusions CRediT authorship contribution statement Declaration of competing interest Acknowledgements Appendix A. Supplementary material Reference

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Plasma Promotes Dry Reforming Reaction of CH₄ and CO₂ at Room Temperature with Highly Dispersed NiO/γ-Al₂O₃ Catalyst

Plasma is an efficient method that can activate inert molecules such as methane and carbon dioxide in a mild environment to make them reactive. In this work, we have prepared an AE-NiO/γ-Al2O3 catalyst using an ammonia-evaporation method for plasma promoted dry reforming reaction of CO2 and CH4 at room temperature. According to the characterization data of XRD, H2-TPR, TEM, XPS, etc., the AE-NiO/γ-Al2O3 catalyst has higher dispersion, smaller particle size and stronger metal-support interaction than the catalyst prepared by the traditional impregnation method. In addition, the AE-NiO/γ-Al2O3 catalyst also exhibits higher activity in dry reforming reaction. This work provides a feasible reference experience for the research of plasma promoted dry reforming reaction catalysts at room temperature

Plasma Promotes Dry Reforming Reaction of CH4 and CO2 at Room Temperature with Highly Dispersed NiO/γ-Al2O3 Catalyst

Plasma is an efficient method that can activate inert molecules such as methane and carbon dioxide in a mild environment to make them reactive. In this work, we have prepared an AE-NiO/γ-Al2O3 catalyst using an ammonia-evaporation method for plasma promoted dry reforming reaction of CO2 and CH4 at room temperature. According to the characterization data of XRD, H2-TPR, TEM, XPS, etc., the AE-NiO/γ-Al2O3 catalyst has higher dispersion, smaller particle size and stronger metal-support interaction than the catalyst prepared by the traditional impregnation method. In addition, the AE-NiO/γ-Al2O3 catalyst also exhibits higher activity in dry reforming reaction. This work provides a feasible reference experience for the research of plasma promoted dry reforming reaction catalysts at room temperature

The reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of traditional Chinese medicine compound formulations and the differences between Chinese and non-Chinese trials

AbstractBackground: An increasing number of randomized placebo-controlled trials involving traditional Chinese medicine (TCM) compound formulations have been implemented worldwide.Objective: The aim of this study was to assess the reporting quality, scientific rigor, and ethics of randomized placebo-controlled trials of TCM compound formulations and compare these differences between Chinese and non-Chinese trials.Methods: English-language databases included the following: PubMed, OVID, EMBASE, and Science Citation Index Expanded. Chinese-language databases included the following: Chinese Biomedical Literature Database, Wanfang Database, Chinese Scientific and Technological Periodical Database, and the China National Knowledge Infrastructure. All were searched from respective inception to March 2009 to identify randomized placebo-controlled trials involving TCM compound prescriptions. Two reviewers independently assessed the retrieved trials via a modified Consolidated Standard of Reporting Trials (CONSORT) checklist and some evaluation indices that embodied the TCM characteristics or the scientific rigor and ethics of placebo-controlled trials. Trial publishing time was divided into 3 intervals: phase 1 (≤1999); phase 2 (2000–2004); and phase 3 (2005–2009). The number and percentage of trials reporting each item and the corresponding differences between Chinese (mainland China, Hong Kong, and Taiwan) and non-Chinese (eg, Japan, United States, Australia, Korea, and United Kingdom) trials were calculated. Moreover, the influence of trial publishing time on the reporting of CONSORT items and the differences in the number of items reported for each time interval between Chinese and non-Chinese trials were assessed.Results: A total of 324 trials from China and 51 trials from other countries were included. A mean of 39.7% of the CONSORT items across all Chinese trials and 50.2% of the items across all non-Chinese trials were reported. The number of the reported CONSORT items all increased over time in both groups and the gap between Chinese articles and non-Chinese articles gradually decreased. Additionally, of the 324 Chinese articles, 137 (42.28%) reported TCM syndrome type, 113 (34.88%) reported the diagnostic criteria of diseases for TCM, and 69 (21.30%) reported efficacy evaluation indices of TCM. Of the non-Chinese articles, 3 (5.88%) reported TCM syndrome type and 1 (1.96%) reported the diagnostic criteria of diseases and evaluation indices of efficacy for TCM. It was found that 45.37% and 6.17% of Chinese articles reported the standard intervention for the diseases being treated and the emergency plan, respectively, compared with 23.53% and 9.80% for the non-Chinese articles; 33.02% and 10.49% of Chinese articles reported informed consent and ethics committee approval, respectively, compared with 92.16% and 82.35% for the non-Chinese articles. With regard to placebo ethics, 38.89% of the Chinese trials and 23.53% of the non-Chinese trials found it would not be ethically acceptable to use placebo alone in the control group.Conclusions: The data indicate that the reporting quality of the included trials on TCM compounds has improved over time, but still remains poor regardless of Chinese or non-Chinese trials. Across all trials, particularly Chinese trials, the reporting of the CONSORT items was inadequate (39.7%). The difference in the mean number of the reported CONSORT items between Chinese trials and non-Chinese trials narrowed from phase 1 (10.0 vs 13.8) to phase 3 (14.4 vs 17.4). Moreover, a large number of trials, especially non-Chinese trials (94.1%), were lacking syndrome differentiation of TCM. More importantly, in many placebo-controlled trials, especially Chinese trials, the use of placebo was not justified and was ethically contradictory

Xiao Yao San Improves Depressive-Like Behaviors in Rats with Chronic Immobilization Stress through Modulation of Locus Coeruleus-Norepinephrine System

Most research focuses on the hypothalamic-pituitary-adrenal (HPA) axis, hypothalamus-pituitary-thyroid (HPT) axis, and hypothalamus-pituitary-gonadal (HPGA) axis systems of abnormalities of emotions and behaviors induced by stress, while no studies of Chinese herbal medicine such as Xiao Yao San (XYS) on the mechanisms of locus coeruleus-norepinephrine (LC-NE) system have been reported. Therefore, experiments were carried out to observe mechanism of LC-NE system in response to chronic immobilization stress (CIS) and explore the antidepressant effect of XYS. Rat model was established by CIS. LC morphology in rat was conducted. The serum norepinephrine (NE) concentrations and NE biosynthesis such as tyrosine hydroxylase (TH), dopamine-β-hydroxylase (DBH), and corticotrophin-releasing-factor (CRF) in LC were determined. Results showed that there were no discernible alterations in LC in rats. The serum NE concentrations, positive neurons, mean optical density (MOD), and protein levels of TH, DBH, and CRF in model group were significantly increased compared to the control group. But XYS-treated group displayed a significantly decreased in NE levels and expressions of TH, DBH, and CRF compared to the model group. In conclusion, CIS can activate LC-NE system to release NE and then result in a significant decrease in rats. XYS treatment can effectively improve depressive-like behaviors in rats through inhibition of LC-NE neurons activity